The long term goal of this research is to provide a better understanding of metabolic and physical performance of the heart as affected by diabetes-mellitus. Specifically, I will study the regulation of cyclic AMP and glycogen metabolism along with mechanical performance in hearts from normal and diabetic rats to determine if and how these parameters are altered by diabetes. Cardiac metabolism and performance will be studied using the isolated perfused rat heart (non-working and working) which provides the advantage of allowing a study of direct effects on the heart without having to consider secondary interventions. Carbohydrate utilization and metabolism will be studied by looking at the effects of diabetes on regulation of glycogen metabolism by glucose, fatty acids, catecholamines, insulin and glucagon. Metabolic effects will be determined by measuring tissue levels of glucose-6-phosphate, glucose-1-phosphate, and uridine diphosphoglucose, and by measuring incorporation of labeled substrate, protein kinase, synthase phosphatase, glycogen phosphorylase, phosphorylase kinase, phosphorylase phosphatase, adenyl cyclase, and phosphodiesterase. We will also examine the effects of diabetes on regulation of cyclic AMP metabolsim. The physical parameters to be monitored include coronary flow, cardiac output, heart rate and aortic pressures. Metabolic and physical parameters will be determined under normal, anoxic and ischemic conditions. This study will provide new information regarding effects of diabetes on cardiac metabolism and function under normal and simulated infarct (ischemic) conditions. A study of this nature could eventually determine if increased risk of cardiac disease is a direct or secondary effect of diabetes and may result in improved treatment of diabetics. BIBLIOGRAPHIC REFERENCE: Miller, T.B., Rannels, S.R., and Jefferson, L.S., Insulin activation of glycogen synthase in perfused skeletal muscle. Diabetes (1977) 26(Sl): 365.